324
Y. Bai et al.
3.2 Co-Metabolism of Tryptophan and Other Aromatic
Amino Acids
Tryptophan is a common substrate for many host microbe co-metabolites, which
can be categorized into kynurenine-, serotonin-, and indole-related metabolites.
Co-metabolism of tryptophan relates to a variety of neural and immune pathological states, including ASD, depression, Alzheimer’s disease, and many autoimmune
diseases. To study their origin, Olson and coworkers developed a quantitative ex vivo
assay using 6-fluorotryptophan and
19 F-NMR to study the origin of 30 tryptophan
metabolites (Fig. 8). According to their results, some metabolites only emanate from
the liver, while others only come from the feces (Fig. 8). Therefore, the tryptophan
metabolic pathways in the liver and gut microbiota are quite different. In addition,
it has been found that the gut microbiome metabolism is disrupted by antibiotic
treatment, as may be expected [16].
Tryptophan also shares some common biotransformation pathways with other
aromatic amino acids including phenylalanine and tyrosine. A gene cluster in the
gut symbiont Clostridium sporogenes has been observed to transform these aromatic
amino acids into arylpyruvates, which are further oxidized to arylacetates or reduced
to aryllactates, arylacrylates, and arylpropionates. The gene cluster is also found in C.
botulinum, Peptostreptococcus anaerobius, and C. cadaveris, while these metabolites
were found further to affect intestinal permeability and systemic immunity in a mouse
model [17].
3.3 Co-Metabolism of Bile Acids
Another good example of host microbe co-metabolism is the generation and transformation of bile acids. Bile acids are synthesized originally from cholesterol in
hepatocytes. After efficient conjugation to either taurine or glycine, bile acids are
transported out of the hepatocytes and secreted into the small intestine as one of the
principal constituents of bile. In the gut, a ubiquitous microbial enzyme named bile
salt hydrolase cleaves the amide bond and releases the unconjugated bile acid, which
further can undergo various biotransformation steps in different bacteria, including
oxidation, epimerization, 7-dehydroxylation, esterification, and desulfation. At the
terminal ileum, the processed bile acids are absorbed into the blood by passive diffusion and active transport and recycled to the liver via the portal vein, a phenomenon
known as enterohepatic circulation. The co-metabolized bile acids such as DCA and
LCA are conjugated to taurine or glycine along with the host-synthesized bile acids
in the hepatocytes, which has further increased the chemical diversity of bile acids
(Fig. 9) [18].
In classical biochemistry, bile acids are believed to be the solubilizers of lipidsoluble nutrients, which thus facilitate their assimilation. Nevertheless, recent target
identification of bile acids has revealed their systemic endocrine functions in versatile
Y. Bai et al.
3.2 Co-Metabolism of Tryptophan and Other Aromatic
Amino Acids
Tryptophan is a common substrate for many host microbe co-metabolites, which
can be categorized into kynurenine-, serotonin-, and indole-related metabolites.
Co-metabolism of tryptophan relates to a variety of neural and immune pathological states, including ASD, depression, Alzheimer’s disease, and many autoimmune
diseases. To study their origin, Olson and coworkers developed a quantitative ex vivo
assay using 6-fluorotryptophan and
19 F-NMR to study the origin of 30 tryptophan
metabolites (Fig. 8). According to their results, some metabolites only emanate from
the liver, while others only come from the feces (Fig. 8). Therefore, the tryptophan
metabolic pathways in the liver and gut microbiota are quite different. In addition,
it has been found that the gut microbiome metabolism is disrupted by antibiotic
treatment, as may be expected [16].
Tryptophan also shares some common biotransformation pathways with other
aromatic amino acids including phenylalanine and tyrosine. A gene cluster in the
gut symbiont Clostridium sporogenes has been observed to transform these aromatic
amino acids into arylpyruvates, which are further oxidized to arylacetates or reduced
to aryllactates, arylacrylates, and arylpropionates. The gene cluster is also found in C.
botulinum, Peptostreptococcus anaerobius, and C. cadaveris, while these metabolites
were found further to affect intestinal permeability and systemic immunity in a mouse
model [17].
3.3 Co-Metabolism of Bile Acids
Another good example of host microbe co-metabolism is the generation and transformation of bile acids. Bile acids are synthesized originally from cholesterol in
hepatocytes. After efficient conjugation to either taurine or glycine, bile acids are
transported out of the hepatocytes and secreted into the small intestine as one of the
principal constituents of bile. In the gut, a ubiquitous microbial enzyme named bile
salt hydrolase cleaves the amide bond and releases the unconjugated bile acid, which
further can undergo various biotransformation steps in different bacteria, including
oxidation, epimerization, 7-dehydroxylation, esterification, and desulfation. At the
terminal ileum, the processed bile acids are absorbed into the blood by passive diffusion and active transport and recycled to the liver via the portal vein, a phenomenon
known as enterohepatic circulation. The co-metabolized bile acids such as DCA and
LCA are conjugated to taurine or glycine along with the host-synthesized bile acids
in the hepatocytes, which has further increased the chemical diversity of bile acids
(Fig. 9) [18].
In classical biochemistry, bile acids are believed to be the solubilizers of lipidsoluble nutrients, which thus facilitate their assimilation. Nevertheless, recent target
identification of bile acids has revealed their systemic endocrine functions in versatile